Chidamide Plus Envafolimab As Subsequent Treatment in Advanced Non-small Cell Lung Cancer Patients Resistant to Anti-PD-1 Therapy: A Multicohort, Open-label, Phase II Trial with Biomarker Analysis

Overview

Journal Cancer Med

Specialty Oncology

Date 2024 Apr 10

PMID 38597130

Authors

Yaxiong Zhang

Zihong Chen

Yu Liu

Liang Han

Wei Jiang

Qiming Wang

Jianhua Shi

Liqin Lu

Jianying Li

Mingjun Zhang

Yan Huang

Yunpeng Yang

Xue Hou

Li Zhang

Jing Li

Wenfeng Fang

Gang Chen

Affiliations

Soon will be listed here.

Abstract

Background: Combination of chidamide and anti-PD-L1 inhibitor produce synergistic anti-tumor effect in advanced NSCLC patients resistant to anti-PD-1 treatment. However, the effect of chidamide plus envafolimab has not been reported.

Aims: This study aimed to evaluate the efficacy of chidamide plus envafolimab in advanced NSCLC patients resistant toanti-PD-1 treatment.

Materials And Methods: Eligible advanced NSCLC patients after resistant to anti-PD-1 therapy received chidamide and envafolimab. The primary endpoint was objective response rate (ORR). The secondary end points included disease control rate (DCR), progression-free survival (PFS), and safety. The expression of histone deacetylase 2 (HDAC2), PD-L1, and blood TMB (bTMB) was also analyzed.

Results: After a median follow-up of 8.1 (range: 7.6-9.2) months, only two patients achieved partial response. The ORR was 6.7% (2/30), DCR was 50% (15/30), and median PFS (mPFS) was 3.5 (95% confidence interval: 1.9-5.5) months. Biomarker analysis revealed that patients with high-level HDAC2 expression had numerically superior ORR (4.3% vs. 0), DCR (52.2% vs. 0) and mPFS (3.7 vs. 1.4m). Patients with negative PD-L1 had numerically superior DCR (52.2% vs. 33.3%) and mPFS (3.7m vs. 1.8m), so were those with low-level bTMB (DCR: 59.1% vs. 16.7%, mPFS: 3.8 vs.1.9m). Overall safety was controllable.

Discussion: High HDAC2patients showed better ORR, DCR, and PFS. In addition, patient with negative PD-L1 and low-level bTMB had better DCR and PFS. This may be related to the epigenetic function of chidamide. However, the sample size was not big enough, so it is necessary to increase sample size to confirm the conclusion.

Conclusion: Combination of chidamide and envafolimab showed efficacy signals in certain NSCLC patients. But further identification of beneficial population is necessary for precision treatment.

Citing Articles

β-glucan combined with Envafolimab and Endostar as immune rechallenge for metastatic non-small cell lung cancer.

Geng Q, Lu Y, Li D, Qin L, Qi C, Pu X BMC Immunol. 2024; 25(1):60.

PMID: 39271997 PMC: 11401293. DOI: 10.1186/s12865-024-00651-x.

Chidamide plus envafolimab as subsequent treatment in advanced non-small cell lung cancer patients resistant to anti-PD-1 therapy: A multicohort, open-label, phase II trial with biomarker analysis.

Zhang Y, Chen Z, Liu Y, Han L, Jiang W, Wang Q Cancer Med. 2024; 13(7):e7175.

PMID: 38597130 PMC: 11004905. DOI: 10.1002/cam4.7175.

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